Heymann Marie-Françoise, Riet Anne, Le Goff Benoît, Battaglia Séverine, Paineau Jacques, Heymann Dominique
INSERM, ERI 7, Nantes, F-44035, France.
Regul Pept. 2008 Jun 5;148(1-3):46-53. doi: 10.1016/j.regpep.2008.02.004. Epub 2008 Feb 19.
Receptor activator of NF-kappaB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) play essential roles in bone metabolism. RANKL binds to RANK, which is expressed by osteoclasts whereas OPG acts as its decoy receptor blocking the RANK-RANKL interaction. OPG/RANK/RANKL are produced by variety of tissues including epithelial and mesenchymal cells. However, the role of RANKL/OPG in thyroid pathophysiology remains unclear. The aim of this study was to determine the expression pattern of RANK/RANKL/OPG in primary neoplastic thyroid lesions and in lymph node metastases. 27 specimens from total thyroidectomy were studied by immunohistochemistry: 9 papillary carcinomas (PC), 9 medullary carcinomas (MC), 9 macrovesicular adenomas (MA). Immunohistochemical evidence of RANKL was found in 30 % of MC, 22% of PC while RANKL has never been detected in PC. The expression of RANK is closely related to RANKL. OPG was restricted to the cytoplasm of epithelial in 1 MA and 1 MC. In contrast to pathological tissues, any expression of OPG/RANK/RANKL was detected in healthy thyroid tissue. This work reveals for the first time that OPG/RANK/RANKL are expressed in the pathological thyroid gland by follicular cells, by malignant parafollicular cells as well as in metastatic lymph node microenvironment. Thus OPG/RANK/RANKL molecular triad might play a role during pathogenesis of follicular and parafollicular tumors.
核因子κB受体激活剂（RANK）、RANK配体（RANKL）和骨保护素（OPG）在骨代谢中发挥着重要作用。RANKL与破骨细胞表达的RANK结合，而OPG作为其诱饵受体阻断RANK-RANKL相互作用。OPG/RANK/RANKL由包括上皮细胞和间充质细胞在内的多种组织产生。然而，RANKL/OPG在甲状腺病理生理学中的作用仍不清楚。本研究的目的是确定RANK/RANKL/OPG在原发性甲状腺肿瘤病变及淋巴结转移中的表达模式。通过免疫组织化学对27例甲状腺全切除标本进行了研究：9例乳头状癌（PC）、9例髓样癌（MC）、9例大滤泡性腺瘤（MA）。在30%的MC和22%的PC中发现了RANKL的免疫组织化学证据，而在PC中从未检测到RANKL。RANK的表达与RANKL密切相关。OPG局限于1例MA和1例MC上皮细胞的细胞质中。与病理组织相反，在健康甲状腺组织中未检测到OPG/RANK/RANKL的任何表达。这项工作首次揭示OPG/RANK/RANKL在病理性甲状腺中由滤泡细胞、恶性滤泡旁细胞以及转移淋巴结微环境表达。因此，OPG/RANK/RANKL分子三联体可能在滤泡性和滤泡旁肿瘤的发病机制中发挥作用。
